Coimbra Institute of Clinical and Biomedical Research (iCBR), Faculty of Medicine and Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-548 Coimbra, Portugal.
Institute of Physiology, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal.
Int J Mol Sci. 2022 May 18;23(10):5652. doi: 10.3390/ijms23105652.
Curcumin has been suggested as a promising treatment for metabolic diseases, but the high doses required limit its therapeutic use. In this study, a new curcuminoid is synthesised to increase curcumin anti-inflammatory and antioxidant potential and to achieve hypoglycaemic and protective vascular effects in type 2 diabetic rats in a lower dose. In vitro, the anti-inflammatory effect was determined through the Griess reaction, and the antioxidant activity through ABTS and TBARS assays. In vivo, Goto-Kakizaki rats were treated for 2 weeks with the equimolar dose of curcumin (40 mg/kg/day) or curcuminoid (52.4 mg/kg/day). Fasting glycaemia, insulin tolerance, plasma insulin, insulin signalling, serum FFA, endothelial function and several markers of oxidative stress were evaluated. Both compounds presented a significant anti-inflammatory effect. Moreover, the curcuminoid had a marked hypoglycaemic effect, accompanied by higher GLUT4 levels in adipose tissue. Both compounds increased NO-dependent vasorelaxation, but only the curcuminoid exacerbated the response to ascorbic acid, consistent with a higher decrease in vascular oxidative and nitrosative stress. SOD1 and GLO1 levels were increased in EAT and heart, respectively. Altogether, these data suggest that the curcuminoid developed here has more pronounced effects than curcumin in low doses, improving the oxidative stress, endothelial function and glycaemic profile in type 2 diabetes.
姜黄素被认为是治疗代谢性疾病的有前途的药物，但由于所需的高剂量限制了其治疗用途。在这项研究中，合成了一种新的姜黄素类化合物，以提高姜黄素的抗炎和抗氧化潜力，并在 2 型糖尿病大鼠中以较低剂量实现降血糖和保护血管作用。在体外，通过格里斯反应测定抗炎作用，通过 ABTS 和 TBARS 测定法测定抗氧化活性。在体内，用等摩尔剂量的姜黄素（40mg/kg/天）或姜黄素类化合物（52.4mg/kg/天）治疗 Goto-Kakizaki 大鼠 2 周。评估空腹血糖、胰岛素耐量、血浆胰岛素、胰岛素信号、血清游离脂肪酸、内皮功能和几种氧化应激标志物。这两种化合物均表现出显著的抗炎作用。此外，姜黄素类化合物具有明显的降血糖作用，同时脂肪组织中 GLUT4 水平升高。这两种化合物均增加了依赖于 NO 的血管舒张作用，但只有姜黄素类化合物加剧了对抗坏血酸的反应，这与血管氧化和硝化应激的降低更为一致。EAT 和心脏中的 SOD1 和 GLO1 水平分别增加。总之，这些数据表明，与姜黄素相比，这里开发的姜黄素类化合物在低剂量下具有更明显的作用，可改善 2 型糖尿病的氧化应激、内皮功能和血糖谱。
